Michael Feichtinger

Increasing live birth rate by preimplantation genetic screening of pooled polar bodies using array comparative genomic hybridization.

Meiotic errors during oocyte maturation are considered the major contributors to embryonic aneuploidy and failures in human IVF treatment. Various technologies have been developed to screen polar bodies, blastomeres and trophectoderm cells for chromosomal aberrations. Array-CGH analysis using bacterial artificial chromosome (BAC) arrays is widely applied for preimplantation genetic diagnosis (PGD) using single cells. Recently, an increase in the pregnancy rate has been demonstrated using array-CGH to evaluate trophectoderm cells. However, in some countries, the analysis of embryonic cells is restricted by law. Therefore, we used BAC array-CGH to assess the impact of polar body analysis on the live birth rate. A disadvantage of polar body aneuploidy screening is the necessity of the analysis of both the first and second polar bodies, resulting in increases in costs for the patient and complex data interpretation. Aneuploidy screening results may sometimes be ambiguous if the first and second polar bodies show reciprocal chromosomal aberrations. To overcome this disadvantage, we tested a strategy involving the pooling of DNA from both polar bodies before DNA amplification. We retrospectively studied 351 patients, of whom 111 underwent polar body array-CGH before embryo transfer. In the group receiving pooled polar body array-CGH (aCGH) analysis, 110 embryos were transferred, and 29 babies were born, corresponding to live birth rates of 26.4% per embryo and 35.7% per patient. In contrast, in the control group, the IVF treatment was performed without preimplantation genetic screening (PGS). For this group, 403 embryos were transferred, and 60 babies were born, resulting in live birth rates of 14.9% per embryo and 22.7% per patient. In conclusion, our data show that in the aCGH group, the use of aneuploidy screening resulted in a significantly higher live birth rate compared with the control group, supporting the benefit of PGS for IVF couples in addition to the suitability and effectiveness of our polar body pooling strategy.

Non-invasive preimplantation genetic screening using array comparative genomic hybridization on spent culture media: a proof-of-concept pilot study

The aim of this pilot study was to assess if array comparative genomic hybridization (aCGH), non-invasive preimplantation genetic screening (PGS) on blastocyst culture media is feasible. Therefore, aCGH analysis was carried out on 22 spent blastocyst culture media samples after polar body PGS because of advanced maternal age. All oocytes were fertilized by intracytoplasmic sperm injection and all embryos underwent assisted hatching. Concordance of polar body analysis and culture media genetic results was assessed. Thirteen out of 18 samples (72.2%) revealed general concordance of ploidy status (euploid or aneuploid). At least one chromosomal aberration was found concordant in 10 out of 15 embryos found to be aneuploid by both polar body and culture media analysis. Overall, 17 out of 35 (48.6%) single chromosomal aneuploidies were concordant between the culture media and polar body analysis. By analysing negative controls (oocytes with fertilization failure), notable maternal contamination was observed. Therefore, non-invasive PGS could serve as a second matrix after polar body or cleavage stage PGS; however, in euploid results, maternal contamination needs to be considered and results interpreted with caution.

Fertility preservation in women with cervical, endometrial or ovarian cancers

BackgroundAlthough cancer in general affects an aged population, a significant number of women develop cancer at childbearing age. Long-term survival rates after gynecological cancer, especially in young patients are increasing and all quality-of-life aspects, including preservation of fertility have become of major relevance.OutcomesSurgical techniques aimed at sparing reproductive organs and preserving fertility have been developed for women presenting with gynecological cancer found at early stages. Indications for fertility-sparing surgery are in general restricted to women presenting with a well-differentiated low-grade tumor in its early stages or with low malignant potential. Up to now, use of fertility-sparing techniques in well-selected patients has not been shown to affect overall survival negatively and fertility outcomes reported have been favorable. Still larger amounts of data and longer follow-up periods are needed. Several current fertility-sparing cancer treatments may result in sub-fertility and in those cases assisted reproductive techniques are indicated. Overall quality of life has been satisfactory in cancer patients after fertility-sparing surgery.ConclusionsFertility-sparing surgery is a viable tool to enable gynecological cancer patients of young age to fulfill their family building without impairment of oncological outcome. Cancer patients of reproductive age should undergo fertility counseling to analyze this sensitive subject. Further studies are needed to investigate the role of fertility-sparing treatment and combined adjuvant therapy in higher-grade cancers.

To Assess the Association between Glucose Metabolism and Ectopic Lipid Content in Different Clinical Classifications of PCOS.

Aims There are emerging data indicating an association between PCOS (polycystic ovary syndrome) and metabolic derangements with potential impact on its clinical presentation. This study aims to evaluate the pathophysiological processes beyond PCOS with particular focus on carbohydrate metabolism, ectopic lipids and their possible interaction. Differences between the two established classifications of the disease should be additionally evaluated. Methods A metabolic characterization was performed in 53 untreated PCOS patients as well as 20 controls including an extended oral glucose tolerance test (OGTT, to assess insulin sensitivity, secretion and ß-cell function) in addition to a detailed examination of ectopic lipid content in muscle and liver by nuclear magnetic resonance spectroscopy. Results Women with PCOS classified by the original NIH 1990 definition showed a more adverse metabolic risk profile compared to women characterized by the additional Rotterdam 2003 phenotypes. Subtle metabolic derangements were observed in both subgroups, including altered shapes of OGTT curves, impaired insulin action and hyperinsulinemia due to increased secretion and attenuated hepatic extraction. No differences were observed for ectopic lipids between the groups. However, particularly hepatocellular lipid content was significantly related to clinical parameters of PCOS like whole body insulin sensitivity, dyslipidemia and free androgen index. Conclusions Subtle alterations in carbohydrate metabolism are present in both PCOS classifications, but more profound in subjects meeting the NIH 1990 criteria. Females with PCOS and controls did not differ in ectopic lipids, however, liver fat was tightly related to hyperandrogenism and an adverse metabolic risk profile.

Reproductive outcome in European and Middle Eastern/North African patients

The aim of this retrospective cohort study was to assess differences in infertility-related baseline characteristics and IVF outcome between European and Middle Eastern/North African (MENA) patients. Of 2703 patients undergoing their first IVF cycle, 2485 were Caucasian of European descent and 218 originated from the MENA region. MENA patients were significantly younger (30.6 versus 34.0 years, P < 0.001), less likely smokers, with higher body mass indexes. Infertility duration was longer in MENA patients (P < 0.001), their male partners were younger (P < 0.001) and smoked more often than European male patients (P = 0.005). Male factor infertility (P = 0.017) and polycystic ovary syndrome (PCOS; P = 0.032) was more prevalent in MENA patients, showed significantly higher basal FSH concentrations (P = 0.012) and significantly fewer oocytes retrieved (RR 0.83, 95% CI 0.74-0.93, P = 0.001). Clinical pregnancy rates were comparable (22.4% [European] versus 22.9% [MENA]). Fewer MENA patients had surplus embryos cryopreserved (OR 0.41, 95% CI 0.22-0.76, P = 0.004). Despite younger age and higher prevalence of PCOS, MENA patients had significantly lower oocyte yields than their European counterparts (P = 0.001). These findings suggest a more rapid decline in ovarian function in women of MENA descent.

Metabolische und reproduktionsmedizinische Aspekte des Polyzystischen Ovarsyndroms (PCOS)

ZusammenfassungDas polyzystische Ovarsyndrom ist die häufigste endokrine Störung von Frauen im reproduktiven Alter. Symptome beinhalten metabolische, gynäkologische und kosmetische Aspekte. Genetische Faktoren leisten einen großen Beitrag zur Manifestation der Erkrankung. So haben männliche Verwandte von PCOS Patientinnen ähnliche Symptome. Eine zentrale Rolle spielen Lebensstilfaktoren, die die klinische Erscheinung des Syndroms wesentlich beeinflussen. Im folgenden Artikel soll ein Überblick über Epidemiologie, metabolische und gynäkologische Aspekte, gender- und genetische Faktoren sowie Therapie von PCOS geliefert werden.SummaryPolycystic ovarian syndrome represents the most common endocrine disease of women of reproductive age. Symptoms include metabolic, gynecologic and cosmetic features. Genetic factors seem to contribute to the disease, affecting not only women but also male relatives of patients with similar symptoms. Besides, lifestyle factors play a central role impacting clinical PCOS appearance. Following we present an overview of the syndrome, its epidemiology, metabolic and gynecological aspects, gender and genetic factors and its therapy.Polycystic ovarian syndrome represents the most common endocrine disease of women of reproductive age. Symptoms include metabolic, gynecologic and cosmetic features. Genetic factors seem to contribute to the disease, affecting not only women but also male relatives of patients with similar symptoms. Besides, lifestyle factors play a central role impacting clinical PCOS appearance. Following we present an overview of the syndrome, its epidemiology, metabolic and gynecological aspects, gender and genetic factors and its therapy.

Morphology of early intrauterine deaths with full trisomy 15

The morphologic features of embryos with full trisomy 15 are described.

Embryoscopy and karyotype findings of repeated miscarriages in recurrent pregnancy loss and spontaneous pregnancy loss

PurposeThe aim of the study was to assess cytogenetic and embryoscopic characteristics in subsequent miscarriages of spontaneous pregnancy losses (SPL) and recurrent pregnancy losses (RPL).MethodsA retrospective cohort of 75 women was affected by repeated pregnancy loss. Of those, 34 had SPL, 24 primary RPL, and 17 secondary RPL. Ploidy status and morphology was analyzed by transcervical embryoscopic examination of the embryo and cytogenetic analysis of the chorionic villi in subsequent miscarriages.ResultsSimilar rates of recurrent ploidy status were observed between first and second miscarriage in SPL and RPL (82.4% recurrent ploidy status in SPL, p > 0.999; 73% recurrent ploidy status in RPL, p = 0.227). No difference was found regarding recurrent abnormal morphology between SPL and RPL (p = 0.092). However, secondary RPL resulted significantly more often in recurrent abnormal morphology compared to primary RPL (p = 0.004).ConclusionsHigh rates of recurrent normal/abnormal karyotypes were observed in all groups with a majority of embryos presenting with recurrent abnormal morphology. Secondary RPL presented significantly more often with recurrent abnormal morphology compared to primary RPL. These findings offer prognostic information for the affected patient and might impact treatment choice.

Allogeneic ovarian transplantation using immunomodulator preimplantation factor (PIF) as monotherapy restored ovarian function in olive baboon

PurposeAllogeneic ovarian transplantation may be an alternative in the future to oocyte donation in women with premature ovarian failure. The objectives of this study were to (a) evaluate allotransplantation feasibility for restoration of ovarian function and (b) assess efficacy of synthetic preimplantation factor (PIF) monotherapy as sole immune-acceptance regimen.MethodsThis is an experimental animal study using non-human primates (Papio anubis). Allogeneic orthotopic ovarian tissue transplantation was performed in two female olive baboons. PIF was administered as a monotherapy to prevent immune rejection and achieve transplant maintenance and function. Subjects underwent bilateral oophorectomy followed by cross-transplantation of prepared ovarian cortex. Postoperatively, subjects were monitored for clinical and biochemical signs of graft rejection and return of function. Weekly blood samples were obtained to monitor graft acceptance and endocrine function restoration.ResultsPostoperatively, there were no clinical signs of rejection. Laboratory parameters (alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine) did not indicate organ rejection at any stage of the experiment. Initially, significant loss of follicles was noticed after grafting and serum follicle-stimulating hormone (FSH) and E2 levels were consistent with ovarian failure. Seven months after transplantation, one animal exhibited recurrence of ovarian endocrine function (perineal swelling, E2 rise, FSH decrease, and return of menstruation).ConclusionsOrgan rejection after allogeneic ovarian transplantation was prevented using PIF as monotherapy for the first time and no side effects were recorded. The study suggests the clinical feasibility of ovarian allotransplantation to obtain ovarian function.

Pre- and peripartal management of a woman with McArdle disease: a case report

Abstract McArdle disease or glycogen storage disease (GSD) type V is a rare autosomal recessive inherited disorder in skeletal muscle metabolism leading to exercise intolerance, muscle cramps and in some cases to rhabdomyolysis and acute renal failure due to elevated serum myoglobin levels. Albeit the uterine smooth muscle is not affected, pregnancy and delivery can be physically strenuous and may require specific anesthesiologic care. However, data on pregnancy progress and outcome and on special implications linked to anesthesia in women with McArdle’s disease is scarce, thus posing a challenge to pre- and peripartal management. We report a case of a pregnant woman with Morbus McArdle who was monitored during her pregnancy and delivered a healthy male via cesarean section under spinal anesthesia. Pregnancy, delivery and recovery were uneventful. Our findings, combined with a literature review, lead to the conclusion that uncomplicated pregnancy and delivery can be expected.